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Abstract:

A method of treating a patient with an ailment, comprises delivering
ultrasound energy to a dorsal root ganglia (DRG), thereby modulating the
DRG to treat the ailment.

Claims:

1. A method of treating a patient with an ailment, comprising: delivering
ultrasound energy to a dorsal root ganglia (DRG), thereby modulating the
DRG to treat the ailment.

2. The method of claim 1, wherein the ultrasound energy has a frequency
in the range of 20 KHz-2 MHz.

3. The method of claim 1, wherein the ultrasound energy has a frequency
in the range of 20 KHz-100 KHz, thereby heating the DRG.

4. The method of claim 1, wherein the ultrasound energy has a frequency
greater than 1 MHz, thereby increasing blood flow to the DRG.

5. The method of claim 1, further comprising delivering a pharmacological
agent to the DRG, thereby further modulating the DRG to treat the
ailment.

6. The method of claim 5, wherein the delivery of the ultrasound energy
induces sonicphoresis for the pharmacological agent in the DRG.

7. The method of claim 1, wherein the ultrasound energy is epidurally
delivered to the DRG.

8. The method of claim 1, wherein the ultrasound energy is delivered from
at least one ultrasonic transducer implanted within the patient.

9. The method of claim 8, wherein the at least one ultrasonic transducer
comprises an array of ultrasonic transducers.

10. The method of claim 1, further comprising delivering ultrasound
energy to a central neural axon extending from the DRG, thereby
modulating the central neural axon to treat the ailment.

11. The method of claim 1, further comprising delivering the ultrasound
energy to a peripheral neural axon extending from the DRG, thereby
modulating the peripheral neural axon to treat the ailment.

12. The method of claim 1, wherein the ailment is pain.

Description:

RELATED APPLICATION DATA

[0001] The present application claims the benefit under 35 U.S.C.
§119 to U.S. provisional patent application Ser. No. 61/652,840,
filed May 29, 2012. The foregoing application is hereby incorporated by
reference into the present application in its entirety.

FIELD OF THE INVENTION

[0002] The present invention relates to tissue modulation systems, and
more particularly, to a system and method for therapeutically modulating
nerve fibers.

BACKGROUND OF THE INVENTION

[0003] Among many techniques attempted for neurostimulation (e.g.,
electrical, chemical, mechanical, thermal, magnetic, optical, and so
forth), electrical stimulation is the standard and most common technique.
Implantable electrical stimulation systems have proven therapeutic in a
wide variety of diseases and disorders. Pacemakers and Implantable
Cardiac Defibrillators (ICDs) have proven highly effective in the
treatment of a number of cardiac conditions (e.g., arrhythmias). Spinal
Cord Stimulation (SCS) techniques, which directly stimulate the spinal
cord tissue of the patient, have long been accepted as a therapeutic
modality for the treatment of chronic pain syndromes, and the application
of spinal cord stimulation has begun to expand to additional
applications, such as angina pectoralis and incontinence. Deep Brain
Stimulation (DBS) has also been applied therapeutically for well over a
decade for the treatment of refractory chronic pain syndromes, and DBS
has also recently been applied in additional areas such as movement
disorders and epilepsy. Further, Functional Electrical Stimulation (FES)
systems such as the Freehand system by NeuroControl (Cleveland, Ohio)
have been applied to restore some functionality to paralyzed extremities
in spinal cord injury patients. Occipital Nerve Stimulation (ONS), in
which leads are implanted in the tissue over the occipital nerves, has
shown promise as a treatment for various headaches, including migraine
headaches, cluster headaches, and cervicogenic headaches. In recent
investigations, Peripheral Stimulation (PS), which includes Peripheral
Nerve Field Stimulation (PNFS) techniques that stimulate nerve tissue
directly at the symptomatic site of the disease or disorder (e.g., at the
source of pain), and Peripheral Nerve Stimulation (PNS) techniques that
directly stimulate bundles of peripheral nerves that may not necessarily
be at the symptomatic site of the disease or disorder, has demonstrated
efficacy in the treatment of chronic pain syndromes and incontinence, and
a number of additional applications are currently under investigation.
Vagal Nerve Stimulation (VNS), which directly stimulate the Vagal Nerve,
has been shown to treat heart failure, obesity, asthma, diabetes, and
constipation.

[0004] Each of these implantable stimulation systems typically includes at
least one stimulation lead implanted at the desired stimulation site and
neurostimulator (e.g., an implantable pulse generator (IPG)) implanted
remotely from the stimulation site, but coupled either directly to the
electrode lead(s) or indirectly to the stimulation lead(s) via a lead
extension. Thus, electrical pulses can be delivered from the
neurostimulator to the stimulation lead(s) to stimulate or activate a
volume of neural tissue. In particular, electrical energy conveyed
between at least one cathodic electrode and at least one anodic electrode
creates an electrical field, which when strong enough, depolarizes (or
"stimulates") the neurons beyond a threshold level, thereby inducing the
firing of action potentials (APs) that propagate along the neural fibers.
The stimulation regimen will typically be one that provides stimulation
energy to all of the target tissue that must be stimulated in order to
provide the therapeutic benefit, yet minimizes the volume of non-target
tissue that is stimulated.

[0005] The stimulation system may further comprise a handheld remote
control (RC) to remotely instruct the neurostimulator to generate
electrical stimulation pulses in accordance with selected stimulation
parameters. The RC may, itself, be programmed by a technician attending
the patient, for example, by using a Clinician's Programmer (CP), which
typically includes a general purpose computer, such as a laptop, with a
programming software package installed thereon. If the IPG contains a
rechargeable battery, the stimulation system may further comprise an
external charger capable of transcutaneously recharging the IPG via
inductive energy.

[0006] Recently, there has been an interest in stimulating dorsal root
ganglia (DRG) for the treatment of chronic pain. The DRG is a nodule that
contains cell bodies of neurons of afferent spinal nerves, and in
particular, dorsal root (DR) nerve fibers. Afferent spinal nerves provide
sensory information (such as touch, pain, heat/cold, and proprioceptive
sensation) which is propagated by action potentials that travel along the
nerve fibers. As shown in FIG. 1, a DRG 1 comprises cell bodies 2 (or
somas) that include axon branches projecting to central and peripheral
targets. In particular, each cell body 2 is typically connected to a stem
neural axon 3 that is branched to a central neural axon 4 (i.e., a spinal
nerve) that extends to the spinal cord, and a peripheral neural axon 5
that extends to a peripheral region of the human body. The positioning of
the cell body 2 is somewhat midway between the central neural axon 4 and
the peripheral neural axon 5, and thus, may be called "pseudounipolar."

[0007] Traditionally, a cell soma provides metabolic support, but DRG soma
are known to undergo subthreshold depolarization when neighbor soma are
invaded with afferent spikes. This means that some degree of cross-talk
between the cell bodies mayoccur in the DRG. In healthy DRG, these
interactions tend to be causal, in that regular afferent activity will
generate subthreshold oscillations and some spiking while the afferent
signaling is present, but rarely when sensory neurons are quiet. In
pathological states, such as those following nerve injury or trauma, it
is believed that the DRG soma become hyperactive, such that they generate
enhanced periodic subthreshold membrane oscillations, often independent
of afferent activity. In the hyperactive state, the soma have increased
metabolic needs, and these needs may lead to oxygen debt and reduced
mitochrondrial performance with the sensory neurons. This, in turn, can
lead to ectopic electrical spiking within the sensory neurons. The action
potentials resulting from the ectopic electrical spiking then feed into
the dorsal horn laminae and are believed to hypersensitize these neural
structures. This hypersensitization may then lead to chronic pain.

[0009] In accordance with the present inventions, a method of treating a
patient with an ailment (e.g., pain) is provided. The method comprises
delivering (e.g., epidurally) ultrasound energy to a dorsal root ganglia
(DRG), thereby modulating the DRG to treat the ailment. The ultrasound
energy may have a frequency in the range of 20 KHz-2 MHz. The ultrasound
energy may be delivered from at least one ultrasonic transducer implanted
within the patient. The ultrasonic transducer may comprise an array of
ultrasonic transducers. In one method, the frequency of the ultrasound
energy is relatively low (e.g., in the range of 20 KHz-100 KHz), thereby
heating the DRG. In another method, the frequency of the ultrasound
energy is relatively high (e.g., greater than 1 MHz), thereby increasing
blood flow to the DRG. An optional method further comprises delivering a
pharmacological agent to the DRG, thereby further modulating the DRG to
treat the ailment. In this case, the delivery of the ultrasound energy
may induce sonicphoresis for the pharmacological agent in the DRG.
Another optional method further comprises delivering ultrasound energy to
a central neural axon and/or peripheral neural axon extending from the
DRG, thereby modulating the central neural axon and/or peripheral neural
axon to treat the ailment.

[0010] Other and further aspects and features of the invention will be
evident from reading the following detailed description of the preferred
embodiments, which are intended to illustrate, not limit, the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The drawings illustrate the design and utility of preferred
embodiments of the present invention, in which similar elements are
referred to by common reference numerals. In order to better appreciate
how the above-recited and other advantages and objects of the present
inventions are obtained, a more particular description of the present
inventions briefly described above will be rendered by reference to
specific embodiments thereof, which are illustrated in the accompanying
drawings. Understanding that these drawings depict only typical
embodiments of the invention and are not therefore to be considered
limiting of its scope, the invention will be described and explained with
additional specificity and detail through the use of the accompanying
drawings in which:

[0013]FIG. 2 is a plan view of one embodiment of a neuromodulation system
arranged in accordance with the present inventions;

[0014]FIG. 3-3A are plan views of a fully implantable modulator (FIM) and
catheter used in the neuromodulation stimulation system of FIG. 2;

[0015]FIG. 4 is front view of a remote control (RC) used in the
neuromodulation system of FIG. 2;

[0016]FIG. 5 is a block diagram of the internal components of the RC of
FIG. 4;

[0017]FIG. 6 is a plan view of the neuromodulation system of FIG. 2 in
use within the spinal column a patient for treating chronic pain; and

[0018]FIG. 7 is a cross-sectional view of the use of the catheter of FIG.
3 for modulating a dorsal root ganglion (DRG).

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0019] Turning first to FIG. 2, an exemplary neuromodulation system 10 is
used to ultrasonically and optionally pharmacologically modulate the
dorsal root ganglion (DRG) and surrounding neural structures. The system
10 generally includes an ultrasonic/drug delivery catheter 12, a fully
implantable modulator (FIM) 14, an external control device in the form of
a remote controller (RC) 16, a clinician's programmer (CP) 18, an
external trial modulator (ETM) 20, and an external charger 22.

[0020] The catheter 12 includes one or more ultrasonic transducers 26,
which emit ultrasound energy when excited by electrical energy.
Ultrasound energy is a mechanical wave in frequencies beyond human
hearing. The catheter 12 also includes one or more drug delivery ports 27
from which a pharmacological agent may be delivered. The FIM 14 is
physically connected to the catheter 12. As will be described in further
detail below, the FIM 14 delivers appropriate electrical energy to the
ultrasonic transducer(s) 26 in accordance with a set of ultrasound
neuromodulation parameters, as well as a pharmacological agent to the
drug delivery port 27 in accordance with drug delivery parameters.
Although only one catheter 12 is shown, multiple ultrasonic/drug delivery
catheters may be connected to the FIM 14.

[0021] The ETM 20 may also be physically connected to the catheter 12. The
ETM 20, which has similar components as that of the FIM 14, also delivers
the ultrasound energy to the ultrasonic transducer(s) 26 and a
pharmacological agent to the drug delivery port 27. The major difference
between the ETM 20 and the FIM 14 is that the ETM 20 is a non-implantable
device that is used on a trial basis after the catheter 12 has been
implanted and prior to implantation of the FIM 14, to test the
responsiveness of the neuromodulation that is to be provided. Thus, any
functions described herein with respect to the FIM 14 can likewise be
performed with respect to the ETM 20.

[0022] The RC 16 may be used to telemetrically control the ETM 20 via a
bi-directional RF communications link 32. Once the FIM 14 and
neuromodulation leads 12 are implanted, the RC 16 may be used to
telemetrically control the FIM 14 via a bi-directional RF communications
link 34. Such control allows the FIM 14 to be turned on or off and to be
programmed with different neuromodulation parameter sets. The FIM 14 may
also be operated to modify the programmed neuromodulation parameters to
actively control the characteristics of the ultrasound
energy/pharmacological agent output by the FIM 14 to the ultrasonic
transducer(s) 26 and drug delivery port 27.

[0023] The CP 18 provides clinician detailed neuromodulation parameters
for programming the FIM 14 and ETM 20 in the operating room and in
follow-up sessions. The CP 18 may perform this function by indirectly
communicating with the FIM 14 or ETM 20, through the RC 16, via an IR
communications link 36. Alternatively, the CP 18 may directly communicate
with the FIM 14 or ETM 20 via an RF communications link (not shown). The
clinician detailed neuromodulation parameters provided by the CP 18 are
also used to program the RC 16, so that the neuromodulation parameters
can be subsequently modified by operation of the RC 16 in a stand-alone
mode (i.e., without the assistance of the CP 18). The external charger 22
is a portable device used to transcutaneously charge the FIM 14 via an
inductive link 38. Once the FIM 14 has been programmed, and its power
source has been charged by the external charger 22 or otherwise
replenished, the FIM 14 may function as programmed without the RC 16 or
CP 18 being present.

[0024] For purposes of brevity, the details of the CP 18, ETM 20, and
external charger 22 will not be described herein. Details of exemplary
embodiments of these devices are disclosed in U.S. Pat. No. 6,895,280,
which is expressly incorporated herein by reference.

[0025] Referring to FIG. 3, the FIM 14 comprises an outer case 40 for
housing the electronic and other components (described in further detail
below). The outer case 40 is composed of an electrically conductive,
biocompatible material, such as titanium, and forms a hermetically sealed
compartment wherein the internal electronics are protected from the body
tissue and fluids. The FIM 14 comprises an ultrasound generator 42
configured for generating electrical pulses for exciting the ultrasonic
transducer(s) 26 on the catheter 12, and a drug pump 44 configured for
conveying a pharmacological agent (e.g., an anesthetic, such as
lidocaine, bupivacain, ropivacaine, and chloroprocaine, and/or an opioid,
such as morphine, fentanyl, sufentanil, or pethidine) stored in a
reservoir 46 to the drug delivery port 27 on the catheter 12. The
ultrasound generator 42 is capable of generating electrical pulses in the
ultrasound range (20 Khz-2 MHz), which electrical pulses will ultimately
be emitted as ultrasound energy by the ultrasonic transducer(s) 26 on the
catheter 12. The ultrasound generator 42 may generate the electrical
pulses as a pulse train, or in continuous fashion, or in a burst fashion
in the range of a few microseconds to several minutes. The drug pump 44
is capable of delivering the pharmacological agent at an adjustable bolus
rate in the range of 0.1-24 mL/per day.

[0026] The FIM 14 may optionally include an external sealed port access 48
for refilling the reservoir 46 with a pharmacological agent using a
hypodermic needle (not shown). Alternatively, if a drug pump is not
available, the hypodermic needle may be used to directly supply a
pharmacological agent via to the port access 48 to the drug delivery port
27 on the catheter 12.

[0027] The FIM 14 further comprises a microcontroller 50 carrying out a
program function in accordance with a suitable program stored in memory
(not shown). Thus, the microcontroller 50 generates the necessary control
and status signals, which allow the microcontroller 50 to control the
operation of the FIM 14 in accordance with a selected operating program
and neuromodulation parameters. In accordance with neuromodulation
parameters stored within the memory, the microcontroller 50 may control
the amplitude and frequency of electrical pulses generated by the
ultrasound generator 42, as well as the drug delivery rate of the drug
pump 44. The memory also store a schedule for periodically delivering the
therapeutic ultrasound energy and/or pharmacological agent.

[0028] The FIM 14 further comprises telemetry circuitry 52 (including
antenna) configured for receiving programming data (e.g., the operating
program and/or neuromodulation parameters) from the RC 16 in an
appropriate modulated carrier signal, and demodulating the carrier signal
to recover the programming data, which programming data is then stored
within the memory. The telemetry circuitry 52 also provides status data
to the RC 16.

[0029] The FIM 14 further comprises a rechargeable power source 54 for
providing the operating power to the FIM 14. The rechargeable power
source 54 may, e.g., comprise a lithium-ion or lithium-ion polymer
battery. The rechargeable power source 54 is recharged using rectified AC
power (or DC power converted from AC power through other means, e.g.,
efficient AC-to-DC converter circuits, also known as "inverter circuits")
received by an AC receiving coil (not shown). To recharge the power
source 54, the external charger 22 (shown in FIG. 2), which generates the
AC magnetic field, is placed against, or otherwise adjacent, to the
patient's skin over the implanted FIM 14. The AC magnetic field emitted
by the external charger 22 induces AC currents in the AC receiving coil.
Charging circuitry (not shown) rectifies the AC current to produce DC
current, which is used to charge the power source 54.

[0030] It should be noted that rather than having a fully contained FIM,
the system 10 may alternatively utilize an implantable receiver-modulator
(not shown) connected to the catheter 12. In this case, the power source,
e.g., a battery, for powering the implanted receiver, as well as control
circuitry to command the receiver-stimulator, will be contained in an
external controller inductively coupled to the receiver-stimulator via an
electromagnetic link. Data/power signals are transcutaneously coupled
from a cable-connected transmission coil placed over the implanted
receiver-modulator. The implanted receiver-modulator receives the signal
and delivers the therapy in accordance with the control signals.

[0031] The FIM 14 further comprises a connector 56 to which the catheter
12 mates in a manner that couples the ultrasonic transducer(s) 26 and
drug delivery port 27 to the internal components within the outer case
40. To this end, the connector 56 includes a port 58 (shown in phantom)
for receiving the proximal end of the catheter 12.

[0032] The catheter 12 includes an elongated catheter body 60 having a
proximal end 62 and a distal end 64. The catheter body 60 may, e.g., have
a diameter within the range of 0.03 inches to 0.07 inches and a length
within the range of 10 cm to 90 cm. The catheter body 60 may be composed
of a suitable electrically insulative material, such as, a polymer (e.g.,
polyurethane or silicone), and may be extruded from as a unibody
construction.

[0033] The catheter 12 includes the ultrasonic transducer(s), which in the
illustrated embodiment, takes the form of a transducer array 26
circumferentially disposed around the distal end 64 of the body 60 for
emitting ultrasound energy in the radial direction. As such, the delivery
of the ultrasound energy to the DRG is not influenced by the rotation of
the catheter 12 relative to the DRG. That is, active ultrasound
transducer may be directed towards the DRG, but if catheter rotation
occurs, this misdirection of the ultrasound energy may be corrected by
selecting a different ultrasound transducer that is directed towards the
DRG after the catheter 12 has rotated. Alternatively, the multiple
radially oriented ultrasonic transducers may be driven at different
intensities (sonic pressure) levels and/or frequencies to implement a
form of "ultrasound steering" where the peak sonic pressure level is
administered at a point between the ultrasonic transducers.

[0034] The catheter 12 further comprises the drug delivery port 27 from
which the pharmacological agent is delivered. The drug delivery port 27
is located on one side of the catheter body 60. Alternatively, multiple
drug delivery ports 27 may be arranged around the circumference of the
catheter body 60 in much the same as the radially-oriented ultrasonic
transducers 26.

[0035] The catheter 12 further comprises a connector (not shown) mounted
to the proximal end 62 of the catheter body 60, which mates with the
connector 56 of the FIM 14 for respectively coupling the ultrasound
generator 42 and drug pump 44 to the ultrasonic transducer(s) 26 and drug
delivery port 27 mounted to the distal end 64 of the catheter body 60.

[0036] As shown in FIG. 3A, the catheter 12 further comprises a plurality
of electrical conductors 66 housed within individual lumens 68 extending
within the catheter body 60 between the connector (not shown) carried by
the proximal end 62 of the catheter body 60 and the transducer array 26
carried by the distal end 64 of the catheter body 60 using suitable
means, such as welding. In this manner, the transducers 26 may be
individually and independently excited by the FIM 14. The catheter 12
further comprises a drug lumen 70 extending through the catheter body 60
between the connector (not shown) carried by the proximal end 62 of the
catheter body 60 and the drug delivery port 27 carried by the distal end
64 of the catheter body 60. The catheter 12 further comprises a central
lumen 72 that may be used to accept an insertion stylet (not shown) to
facilitate implantation of the catheter 12. The connector includes
electrical terminals (not shown) hardwired to the respective conductors
66 and capable of mating with corresponding electrical terminals (not
shown) on the connector 56 of the FIM 14 (shown in FIG. 2). Thus,
electrical energy can be conveyed from the FIM 14 to the catheter
connector, along the conductors 66 to the transducer array 26. The
connector includes a fluid coupler (not shown) affixed to the drug lumen
70 and capable of mating with a corresponding fluid coupler on the
connector 56 of the FIM 14 (shown in FIG. 2). Thus, a pharmacological
agent can be conveyed from the FIM 14 to the catheter connector, along
the drug lumen 70 to the drug delivery port 27.

[0037] Referring now to FIG. 4, one exemplary embodiment of an RC 16 will
now be described. As previously discussed, the RC 16 is capable of
communicating with the FIM 14 or CP 18. The RC 16 comprises a casing 100,
which houses internal componentry (including a printed circuit board
(PCB)), and a lighted display screen 102 and button pad 104 carried by
the exterior of the casing 100. In the illustrated embodiment, the
display screen 102 is a lighted flat panel display screen, and the button
pad 104 comprises a membrane switch with metal domes positioned over a
flex circuit, and a keypad connector connected directly to a PCB. In an
optional embodiment, the display screen 102 has touchscreen capabilities.
The button pad 104 includes a multitude of buttons 106, 108, 110, and
112, which allow the FIM 14 to be turned ON and OFF, provide for the
adjustment or setting of neuromodulation parameters within the FIM 14,
and provide for selection between screens.

[0038] In the illustrated embodiment, the button 106 serves as an ON/OFF
button that can be actuated to turn the FIM 140N and OFF. The button 108
serves as a select button that allows the RC 106 to switch between screen
displays and/or parameters. The buttons 110 and 112 serve as up/down
buttons that can be actuated to increase or decrease any of
neuromodulation parameters of the electrical energy generated by the FIM
14, including the amplitude and frequency, which will ultimately be
transformed by the ultrasonic transducer array 26 into ultrasound energy
having intensity (sonic pressure) levels and frequencies dictated by the
amplitude and frequency of the electrical energy generated by the FIM 14.

[0039] The selection button 158 can be actuated to place the RC 16 in an
"Ultrasound Modulation Adjustment Mode," during which any of the
ultrasound neuromodulation parameters, including the amplitude and
frequency, can be selected and adjusted via the up/down buttons 160, 162,
or an "Drug Delivery Adjustment Mode," during which any of the
pharmacological neuromodulation parameters, including the flow rate, can
be selected and adjusted via the up/down buttons 160, 162. Alternatively,
dedicated up/down buttons can be provided for each neuromodulation
parameter. Rather than using up/down buttons, any other type of actuator,
such as a dial, slider bar, or keypad, can be used to increment or
decrement the neuromodulation parameters. Thus, the RC 16 can be used to
program the FIM 14 with the desired intensity and frequency of the
therapeutic ultrasound energy and the desired bolus rate of the drug
delivery in a calibration procedure. The RC 16 may also store information
about the programming/calibration session, as well as uploaded
information from the FIM 14, which can log diagnostics of use over time.

[0040] Referring to FIG. 5, the internal components of an exemplary RC 16
will now be described. The RC 16 generally includes a
controller/processor 114 (e.g., a microcontroller), memory 116 that
stores an operating program for execution by the controller/processor
114, and telemetry circuitry 118 for transmitting control data (including
neuromodulation parameters and requests to provide status information) to
the FIM 14 and receiving status information from the FIM 14 via link 34
(or link 32) (shown in FIG. 2), as well as receiving the control data
from the CP 18 and transmitting the status data to the CP 18 via link 36
(shown in FIG. 2). The RC 16 further includes input/output circuitry 120
for receiving stimulation control signals from the button pad 104 and
transmitting status information to the display screen 102 (shown in FIG.
5). Further details of the functionality and internal componentry of the
RC 16 are disclosed in U.S. Pat. No. 6,895,280, which has previously been
incorporated herein by reference.

[0041] Having described the structure and function of the neuromodulation
system 10, a technique for using the neuromodulation system 10 to treat
patients having pain, which may be chronic, will now be described. In
this method, ultrasound neuromodulation energy is delivered to a dorsal
root ganglia (DRG), thereby modulating the DRG. Modulation of the DRG and
surrounding neural structures modulates the sensory information, such as
pain, touch, heat, and proprioceptive sensation traveling through the
DRG. The effect on the DRG and surrounding neural structures will depend
on the frequency of the ultrasound neuromodulation energy. If the
frequency of the ultrasound neuromodulation energy is relatively low
(e.g., 20 KHz-100 KHz) with a relatively higher sonic pressure level, the
pressure and vibration may induce changes in tensions on the neuronal
membrane of the DRG cell bodies. The voltage gated ion channels may be
sensitive to such mechanical tension changes, thereby changing the
membrane conduction and thus excitability of the cell bodies. If the
frequency of the ultrasound neuromodulation energy is relatively high
(e.g., greater than 1 MHz) with a relatively lower sonic pressure level,
the blood flow to the DRG may be increased, thereby providing more oxygen
and increased mitochondrial performance of the DRG cell bodies. A
pharmacological agent may also be delivered to the DRG as an adjunct to
the delivery of the ultrasound energy. Advantageously, the delivery of
the ultrasound energy to the DRG may improve the sonicphoresis of the
pharmacological agent in the DRG.

[0042] In one method for treating chronic pain, the DRG and optionally the
surrounding neural structures may be modulated by implanting the catheter
12 within the spinal column 132 of a patient 130, as shown in FIG. 6. As
shown in FIG. 7, the preferred placement of the catheter 12 is in the
epidural space 134 of the patient 130. The catheter 12 may be located in
the foramen 136 that extends from the epidural space 134 over the dura
138 covering the DRG 140. In this manner, ultrasound neuromodulation
energy and pharmacological can be conveniently delivered to the DRG 140
and surrounding neural structures. The catheter 12 can conventionally be
introduced, with the aid of fluoroscopy, into the epidural space 134
above the spinal cord 148 through a Touhy-like needle, which passes
through the skin, between the desired vertebrae, and into the epidural
space 134 above the dura 138. In many cases, a stylet, such as a metallic
wire, is inserted into a lumen running through the center of the catheter
12 to aid in insertion of the lead through the needle and into the
epidural space 134. The catheter 12 may then be introduced into the
foramen 136 from the epidural space 134. The stylet gives the lead
rigidity during positioning, and once the catheter 12 is positioned, the
stylet can be removed after which the lead becomes flaccid.

[0043] After proper placement of the catheter 12 at the target area of the
spinal column 132, the catheter 12 is anchored in place to prevent
movement of the catheter 12. The proximal end of the catheter 12 exiting
the spinal column 132 is passed through one or more tunnels (not shown)
subcutaneously formed along the torso of the patient 130 to a
subcutaneous pocket (typically made in the patient's abdominal or buttock
area) where the FIM 14 is implanted. The FIM 14 may, of course, also be
implanted in other locations of the patient's body. A subcutaneous tunnel
can be formed using a tunneling tool over which a tunneling straw may be
threaded. The tunneling tool can be removed, the catheter 12 threaded
through the tunneling straw, and then the tunneling straw removed from
the tunnel while maintaining the catheter 12 in place within the tunnel.

[0044] The catheter 12 is then connected directly to the FIM 14 by
inserting the proximal end of the catheter 12 within the connector port
58 located on the connector 56 of the FIM 14. The FIM 14 can then be
operated to generate the electrical energy for exciting the ultrasonic
transducers 26 and/or delivering the pharmacological agent through the
drug delivery port 27. As there shown, the CP 18 communicates with the
FIM 14 via the RC 16, thereby providing a means to control and reprogram
the FIM 14.

[0045] The ultrasound neuromodulation energy and/or pharmacological agent
may also be delivered from the catheter 12 to neural structures
surrounding the DRG 140, including central neural axon and peripheral
neural axon extending from the DRG 140. In this case, additional
ultrasound transducers and/or drug delivery ports may be provided along
the length of the catheter 12, such that the ultrasound neuromodulation
energy and/or pharmacological agent may be concurrently delivered to both
the DRG and the central neural axon and/or peripheral neural axon. The
delivery of the ultrasound neuromodulation energy and/or pharmacological
agent to either the central neural axon or peripheral neural axon may
depend on the source of the pain. For example, if the source of pain
resides only in the DRG 140, the ultrasound energy and/or pharmacological
agent can be delivered to the both the DRG 140 and the central neural
axon. If the source of pain resides only in the peripheral neural axon,
the ultrasound energy and/or pharmacological agent can be delivered to
the both the DRG 140 and the peripheral neural axon. If the source of
pain resides in both the DRG 140 and the peripheral neural axon, the
ultrasound energy and/or pharmacological agent can be delivered to all
three of the DRG 140, the central neural axon, and the peripheral neural
axon.

[0046] Although particular embodiments of the present inventions have been
shown and described, it will be understood that it is not intended to
limit the present inventions to the preferred embodiments, and it will be
obvious to those skilled in the art that various changes and
modifications may be made without departing from the spirit and scope of
the present inventions. Thus, the present inventions are intended to
cover alternatives, modifications, and equivalents, which may be included
within the spirit and scope of the present inventions as defined by the
claims.